Project 3 - Antibiotic resistance and metabolic pathways in Chlamydia spp This project will focus on key biosynthetic and metabolic functions of Chlamydia as they impact on drug resistance and growth and survival in the host. It consists of three aims: Specific Aim 1 - To model the emergence of resistance to the drugs of choice for the treatment of C. trachomatis infections. We will measure the fitness of azithromycin resistant (AZM*^) mutants in vitro and in vivo. We will then screen for compensatory mutants that arise in vivo and characterize these mutants using whole genome sequencing technology. We will also select for spontaneous tetracycline resistant (Tc*^) mutants of C. caviae (GPIC) in a natural infection model in guinea pigs. The mutants that arise in the natural infection setting will be analyzed for growth characteristics such as growth in tissue culture and competition experiments in vivo and in vitro in the absence of antibiotic. A complement to the animal model studies will be a survey for drug resistant Isolates the clinical setting among